The objectives of the project are to gain insight into: 1) the macromolecular components involved in synapse structure and function; 2) the topographic organization of those proteins; 3) determine whether neural disease results in modification of the proteins in the synapse. Synapses are isolated from human brains obtained 4-12 hours postmortem and the proteins are solubilized with 8 M urea. Proteins are isolated by ion exchange chromatography (DEAE cellulose) and gel filtration (G- 150). The solutions used for purification of the proteins all contain 8 M urea. One of the major components of human and swine synaptic complexes is a 53,000 MW protein. This protein is very similar to tubulin as determined by electrophoresis on 3 different gel systems, molecular weight analyses, peptide mapping procedures and amino acid analyses. Synapses have been isolated from brains of patients that died with various diseases including multiple sclerosis, brain tumors of multiple origin, Hodgkin's disease, leukemias, hamartoma, senile dementia, strokes, suicide, homicide and Tay Sachs disease. The buoyant density of synapses (1.17-1.19) were not altered in any of these diseases with the exception of Tay Sach's disease (1.19-1.20). Synapses were readily recovered from frozen brains (-80 degrees C) and identified ultrastructurally.